Sickle cell

Definition of Terms
• Sickle cell disease (SCD): Denotes all genotypes that contain at least 1 sickle gene, in
which haemoglobin (Hb) S makes up at least half of the Hb present
o In addition to homozygotic HbSS (sickle cell anaemia [SCA]) in which only HbS is
produced, at least 5 other major genotypes are linked to the disease, including:
ƒ HbS– β0 thalassemia- almost indistinguishable from SCA phenotypically
ƒ HbSC disease with intermediate clinical severity
ƒ HbS/hereditary persistence of foetal Hb (S/HPHP) - mild form or symptom free
ƒ HbS/HbE syndrome - rare and generally mild clinical course
ƒ Other rare combinations
ƒ SCA is the most severe and most common form
• Sickle cell anaemia: Originates from inheritance of one copy of the sickle cell gene from
each parent, who may either be heterozygous (Hb AS) or homozygous (Hb SS)
• Sickle cell trait: When one has normal adult Hb A and an abnormal Hb S (i.e.
heterozygous [HbAS])
o These children are asymptomatic
• HbS is a result of the substitution of valine for glutamic acid in position 6 of the beta (ß)
chain of Hb
Note: HbAS offers some protection against falciparum malaria. The infestation of the malaria
plasmodium is halted by the sickling of the cell which it infests.
Characteristics of Red Blood Cells with Abnormal Haemoglobin (HbSS)
• Red blood cells (RBC) are abnormal and have short life span of 8 to 20 days
• Under low oxygen tension (that is when deoxygenated)
o Cells become elliptic (thus the name sickle cell), rigid, sticky and fragile
o Cells clump together and occlude small blood capillaries
Clinical Features of Sickle Cell Anaemia
• Although a diagnosis of the disease can be made at birth, clinical abnormalities usually do
not occur before 6 months
• By the end of childhood, functional asplenia due to repeated sickling of red cells and
ultimately infarction of splenic tissue results in susceptibility to overwhelming infection
with encapsulated organisms such as Streptococcus pneumoniae and Haemophilus
influenzae
• The risk is decreased but still significant even in the vaccinated population

Subsequently, other organs are damaged
• Typical manifestations include recurrent pain and progressive infarction

Figure 1:
Age and Features of Sickle Cell Anaemia

Age.  
0-4 months •
Feature
No features (due to presence of fetal Hb)

>4 months-1 year

Feature
• Pallor
• Dactylitis (hand and foot syndrome)
o Severely painful symmetrical swelling of the hands and feet
caused by infarctions of the small bones
o May be the initial manifestation, is most common in those < 2
years
• Jaundice
• Recurrent infections
• Splenomegaly

2-5 years

Feature
• Pallor
• Jaundice
• Recurrent infections
• Hepatosplenomegaly
• Recurrent infections

>5 years
Feature
• Pallor
• Jaundice
• Bossing of the skull
• Long thin extremities
• Autosplenectomy
• Adolescents may have delayed puberty

Sickle Cell Crises
• Vaso-occlusive (thrombotic) or painful crisis
o The most common form of crisis
o Caused by occlusion of the small blood vessel and restrict blood flow to organs
o This results into ischaemia, pain and organ damage
o Pain in the limbs and joints and tenderness
o Hydration and analgesics are the mainstay of therapy
o If IV fluids needed, give isotonic sodium chloride solution
• Sequestration crisis
o Also called ‘acute or splenic sequestration crisis’
o A medical emergency
o Is specific form of acute hypersplenism in young children
o A large amount of blood is trapped in the spleen causing a sudden fall in Hb
o Children develop painful, rapid and massive splenic enlargement with consumption of
large volumes of erythrocytes
o They present with marked pallor, shock or sudden weakness, dyspnea, and left-sided
abdominal pain in addition to the splenomegaly
o Death due to hypovolemic shock occur rapidly
o Treatment consists of IV fluids and erythrocyte (packed red blood cell) transfusions
o To prevent recurrences, splenectomy may be indicated

o In most patients with SCA, the spleen eventually involutes and sequestration is no
longer a problem
• Acute chest syndrome
o Common cause of morbidity and mortality
o Triggered by painful crises, respiratory infection or surgery
o This condition is characterized by:
ƒ Difficulty breathing
ƒ Tachycardia, tachypnea and hypoxemia are common
ƒ Patients present with a new infiltrate on chest X-ray, often with chest pain and
fever
o Treatment includes oxygen therapy, IV antibiotics, and analgesics
o Simple transfusion administered early may halt progressive respiratory deterioration
• Haemolytic crisis
o Acute accelerated drop in Hb level
o The RBC breaks down at a faster rate
• Aplastic crisis
o Associated with Parvovirus B19 infection
o Depression of the RBC precursors in the bone marrow
o Presents with pallor, tachycardia and fatigue
o Inadequate production of RBC can be life threatening when the RBC life span is short
Hypersplenism
• Hypersplenism is a clinical syndrome in which cytopenias result when splenic function
becomes excessive as the spleen enlarges
• This has been attributed to the following four possible mechanisms
o Excessive splenic phagocytic activity
o Splenic production of antibodies that results in the destruction of hematopoietic cells
o Over activity of splenic function
o Splenic sequestration
• If results in recurrent severe anaemia necessitating repeated blood transfusion,
splenectomy may be indicated (refer to hospital)
Complications and Management
• Avascular necrosis of head of femur
• Autosplenectomy due to repeated infarcts
• Osteomyelitis by salmonella
• Acute papillary necrosis causing haematuria
• Prone to infections due to low immunity
• Chronic ulcers (legs)
• Priapism may occur at any age but more common after puberty
• Cerebral infarction
o Presenting complaint depends on the nature of the event and includes gait disturbance,
aphasia, altered level of consciousness, hemiparesis or hemiplegia or seizures
• Blindness from retinal detachment
• Gallstones (cholelithiasis) because of chronic haemolysis
Management
• Investigations
o Hb range typically 6-8 g/dl
o Sickling test (may be negative if transfused within last 3 months)

o Hb electrophoresis (done at hospital level)
o Full blood picture (FBP) may apart from anaemia, indicate macrocytosis
(megaloblasts or reticulocytes), total white blood cells (WBC) may be high
(leucocytosis)
o In hypersplenism, anaemia, reduced levels of WBC’s and platelets may be seen
o Reticulocytosis (high number of immature RBC’s)
Treatment
• No specific treatment, but the following help to alleviate symptoms
o Prophylaxis with folic acid 5mg daily, and chloroquine 5 mg/kg weekly to prevent
malaria
o Do not give iron as there are plenty of iron stores coming from the destruction of the
Haem group that may actually lead to iron overload
o When a child has malaria, treat with Artemether/Lumefantrine (ALu) or Quinine if
they have severe malaria
o Growth monitoring, immunization and proper nutrition
o Treat other infections vigorously
• For sickle cell crises
o Sickle cell crises are precipitated by fever, dehydration, infection, hypoxia or surgery
o Give analgesics (e.g. paracetamol)
o IV fluids , normal saline or ringer’s lactate
o Treat infections vigorously (give pre-referral antimalaria and antibiotics,( i.e. inj.
quinine 10 mg/kg IM and inj. chloramphenical 25 mg/kg IM respectively)
o Keep warm, and refer to hospital